The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Perinatal exposure of rats to a maternal diet with varying protein quantity and quality affects the risk of overweight in female adult offspring

The maternal protein diet during the perinatal period can program the health of adult offspring. This study in rats evaluated the effects of protein quantity and quality in the maternal diet during gestation and lactation on weight and adiposity in female offspring. Six groups of dams were fed a high-protein (HP; 47% protein) or normal-protein (NP; 19% protein) isocaloric diet during gestation (G) using either cow's milk (M), pea (P) or turkey (T) proteins. During lactation, all dams received the NP diet (protein source unchanged). From postnatal day (PND) 28 until PND70, female pups (n=8) from the dam milk groups were exposed to either an NP milk diet (NPMW) or to dietary self-selection (DSS). All other pups were only exposed to DSS. The DSS design was a choice between five food cups containing HPM, HPP, HPT, carbohydrates or lipids. The weights and food intakes of the animals were recorded throughout the study, and samples from offspring were collected on PND70. During the lactation and postweaning periods, body weight was lower in the pea and turkey groups (NPG and HPG) versus the milk group (P<.0001). DSS groups increased their total energy and fat intakes compared to the NPMW group (P<.0001). In all HPG groups, total adipose tissue was increased (P=.03) associated with higher fasting plasma leptin (P<.05). These results suggest that the maternal protein source impacted offspring body weight and that protein excess during gestation, irrespective of its source, increased the risk of adiposity development in female adult offspring

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Proposal of a Nutritional Quality Index (NQI) to Evaluate the Nutritional Supplementation of Sportspeople

Background: Numerous supplements are used by sportspeople. They are not always appropriate for the individual or the sports activity and may do more harm than good. Vitamin and mineral supplements are unnecessary if the energy intake is sufficient to maintain body weight and derives from a diet with an adequate variety of foods. The study objectives were to evaluate the main nutrients used as supplements in sports and to propose a nutritional quality index (NQI) that enables sportspeople to optimize their use of supplements and detect and remedy possible nutritional deficits. Material and Methods: A nutritional study was performed in 485 sportspeople recruited from Centros Andaluces de Medicina del Deporte, (CAMD). All completed socio-demographic, food frequency, and lifestyle questionnaires. The nutritional quality of their diet and need for supplementation were evaluated by scoring their dietary intake with and without supplementation, yielding two NQI scores (scales of 0-21 points) for each participant. Results: A superior mean NQI score was obtained when the supplements taken by participants were not included (16. 28 (SD of 3.52)) than when they were included (15.47 (SD: 3.08)), attributable to an excessive intake of some nutrients through supplementation. Conclusions: These results indicate that sportspeople with a varied and balanced diet do not need supplements, which appear to offer no performance benefits and may pose a health risk.The authors are grateful to the Junta de Andalucía, Spain (Research Group AGR-255“Nutrition. Diet and Risk Assessment”), a collaboration agreement with the Andalusian Centres of Sports Medicine (Junta de Andalucía) and the FPU program of the Spanish Ministry of Education and Science. Study participants were recruited through the project “Nutritional and diet assessment methodologies applied to the Andalusian sportsperson in Andalusian Sports centres”, Research project FMD2010SC0071 of the Junta de Andalucía

Methyl donor deficient diets cause distinct alterations in lipid metabolism but are poorly representative of human NAFLD

Background: Non-alcoholic fatty liver disease (NAFLD) is a global health issue. Dietary methyl donor restriction is used to induce a NAFLD/non-alcoholic steatohepatitis (NASH) phenotype in rodents, however the extent to which this model reflects human NAFLD remains incompletely understood. To address this, we undertook hepatic transcriptional profiling of methyl donor restricted rodents and compared these to published human NAFLD datasets.              Methods: Adult C57BL/6J mice were maintained on control, choline deficient (CDD) or methionine/choline deficient (MCDD) diets for four weeks; the effects on methyl donor and lipid biology were investigated by bioinformatic analysis of hepatic gene expression profiles followed by a cross-species comparison with human expression data of all stages of NAFLD. Results: Compared to controls, expression of the very low density lipoprotein (VLDL) packaging carboxylesterases (Ces1d, Ces1f, Ces3b) and the NAFLD risk allele Pnpla3 were suppressed in MCDD; with Pnpla3 and the liver predominant Ces isoform, Ces3b, also suppressed in CDD. With respect to 1-carbon metabolism, down-regulation of Chka, Chkb, Pcty1a, Gnmt and Ahcy with concurrent upregulation of Mat2a suggests a drive to maintain S-adenosylmethionine levels. There was minimal similarity between global gene expression patterns in either dietary intervention and any stage of human NAFLD, however some common transcriptomic changes in inflammatory, fibrotic and proliferative mediators were identified in MCDD, NASH and HCC. Conclusions: This study suggests suppression of VLDL assembly machinery may contribute to hepatic lipid accumulation in these models, but that CDD and MCDD rodent diets are minimally representative of human NAFLD at the transcriptional level

Tumor Progression Locus 2 (Tpl2) Deficiency Does Not Protect against Obesity-Induced Metabolic Disease

Obesity is associated with a state of chronic low grade inflammation that plays an important role in the development of insulin resistance. Tumor progression locus 2 (Tpl2) is a serine/threonine mitogen activated protein kinase kinase kinase (MAP3K) involved in regulating responses to specific inflammatory stimuli. Here we have used mice lacking Tpl2 to examine its role in obesity-associated insulin resistance. Wild type (wt) and tpl2−/− mice accumulated comparable amounts of fat and lean mass when fed either a standard chow diet or two different high fat (HF) diets containing either 42% or 59% of energy content derived from fat. No differences in glucose tolerance were observed between wt and tpl2−/− mice on any of these diets. Insulin tolerance was similar on both standard chow and 42% HF diets, but was slightly impaired in tpl2−/− mice fed the 59% HFD. While gene expression markers of macrophage recruitment and inflammation were increased in the white adipose tissue of HF fed mice compared with standard chow fed mice, no differences were observed between wt and tpl2−/− mice. Finally, a HF diet did not increase Tpl2 expression nor did it activate Extracellular Signal-Regulated Kinase 1/2 (ERK1/2), the MAPK downstream of Tpl2. These findings argue that Tpl2 does not play a non-redundant role in obesity-associated metabolic dysfunction

Activation of Pregnane X Receptor by Pregnenolone 16 α-carbonitrile Prevents High-Fat Diet-Induced Obesity in AKR/J Mice

Pregnane X receptor (PXR) is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis. Here we report that the activation of PXR by pregnenolone 16α-carbonitrile (PCN) in AKR/J mice can prevent the development of high-fat diet-induced obesity and insulin resistance. The beneficial effects of PCN treatment are seen with reduced lipogenesis and gluconeogenesis in the liver, and lack of hepatic accumulation of lipid and lipid storage in the adipose tissues. RT-PCR analysis of genes involved in gluconeogenesis, lipid metabolism and energy homeostasis reveal that PCN treatment on high-fat diet-fed mice reduces expression in the liver of G6Pase, Pepck, Cyp7a1, Cd36, L-Fabp, Srebp, and Fas genes and slightly enhances expression of Cyp27a1 and Abca1 genes. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue show that PCN treatment reduces expression of Pparγ2, Acc1, Cd36, but increases expression of Cpt1b and Pparα genes in mice fed with high-fat diet. Similarly, PCN treatment of animals on high-fat diet increases expression in brown adipose tissue of Pparα, Hsl, Cpt1b, and Cd36 genes, but reduces expression of Acc1 and Scd-1 genes. PXR activation by PCN in high-fat diet fed mice also increases expression of genes involved in thermogenesis in brown adipose tissue including Dio2, Pgc-1α, Pgc-1β, Cidea, and Ucp-3. These results verify the important function of PXR in lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention and treatment of obesity and insulin resistance

Effects of orange juice formulation on prebiotic functionality using an in vitro colonic model sytem

A three-stage continuous fermentative colonic model system was used to monitor in vitro the effect of different orange juice formulations on prebiotic activity. Three different juices with and without Bimuno, a GOS mixture containing galactooligosaccharides (B-GOS) were assessed in terms of their ability to induce a bifidogenic microbiota. The recipe development was based on incorporating 2.75g B-GOS into a 250 ml serving of juice (65°Brix of concentrate juice). Alongside the production of B-GOS juice, a control juice - orange juice without any additional Bimuno and a positive control juice, containing all the components of Bimuno (glucose, galactose and lactose) in the same relative proportions with the exception of B-GOS were developed. Ion Exchange Chromotography analysis was used to test the maintenance of bimuno components after the production process. Data showed that sterilisation had no significant effect on concentration of B-GOS and simple sugars. The three juice formulations were digested under conditions resembling the gastric and small intestinal environments. Main bacterial groups of the faecal microbiota were evaluated throughout the colonic model study using 16S rRNA-based fluorescence in situ hybridization (FISH). Potential effects of supplementation of the juices on microbial metabolism were studied measuring short chain fatty acids (SCFAs) using gas chromatography. Furthermore, B-GOS juices showed positive modulations of the microbiota composition and metabolic activity. In particular, numbers of faecal bifidobacteria and lactobacilli were significantly higher when B-GOS juice was fermented compared to controls. Furthermore, fermentation of B-GOS juice resulted in an increase in Roseburia subcluster and concomitantly increased butyrate production, which is of potential benefit to the host. In conclusion, this study has shown B-GOS within orange juice can have a beneficial effect on the fecal microbiota

Towards microbiome-informed dietary recommendations for promoting metabolic and mental health: opinion papers of the MyNewGut project

The gut microbiota coexists in partnership with the human host through adaptations to environmental and physiological changes that help maintain dynamic homeostatic healthy states. Break-down of this delicate balance under sustained exposure to stressors (e.g. unhealthy diets) can, however, contribute to the onset of disease. Diet is a key modifiable environmental factor that modulates the gut microbiota and its metabolic capacities that, in turn, could impact human physiology. On this basis, the diet and the gut microbiota could act as synergistic forces that provide resilience against disease or that speed the progress from health to disease states. Associations between unhealthy dietary patterns, non-communicable diseases and intestinal dysbiosis can be explained by this hypothesis. Translational studies showing that dietary-induced alterations in microbial communities recapitulate some of the pathological features of the original host further support this notion. In this introductory paper by the European project MyNewGut, we briefly summarize the investigations conducted to better understand the role of dietary patterns and food components in metabolic and mental health and the specificities of the microbiome-mediating mechanisms. We also discuss how advances in the understanding of the microbiome's role in dietary health effects can help to provide acceptable scientific grounds on which to base dietary advice for promoting healthy living